Opioid therapy remains a common strategy for severe and chronic pain management with 3-4% of adults in the U.S. receiving long-term opioid therapy (Dowell D, et al. (2016) MMWR Recomm Rep 65:1-49). However, decreased analgesic efficacy over time (i.e., tolerance) significantly impedes treatment for approximately 60% of the patient population (Gulur P, et al. (2014) Pain Physician 17:E503-507). Long-term opioid therapy is associated with increased risk of abuse, dependence, and dose-related fatal overdose (Dowell D, et al. (2016) MMWR Recomm Rep 65:1-49) Immune signaling is a significant contributor to the negative consequences of opioid therapy including tolerance, hyperalgesia, addiction, dependence, and withdrawal (Hutchinson M R, et al. (2007) ScientificWorldJournal 7:98-111), and has been implicated as a driving factor in a variety of chronic pain syndromes, including Rheumatoid arthritis (RA) and fibromyalgia (Heo Y J, et al. (2011) Arthritis Res Ther 13:R113; Kosek E, et al. (2015) J Neuroimmunol 280:49-55).
Currently, morphine tolerance is treated by ibudilast (AV411), minocycline, fluorocitrate, propentofylline. However, these immunomodulatory drugs have widespread and non-specific effects. Thus, significant drawbacks exist with the use of current treatments.
Understanding the mechanisms underlying opioid-induced neuroinflammation is paramount to developing effective pain management strategies that minimize the risk of dependence, abuse, and long-term consequences of chronic neuroinflammation.